Core B: Clinical Project Summary/Abstract Core B: Clinical supports the Adult Children Study (ACS) Program Project Grant (PPG) by recruiting, enrolling and longitudinally following adult children, age 45-74 years at entry, of parents with and without symptomatic Alzheimer disease (AD). ACS participants age 45-64y will have clinical and psychometric assessments at entry and every 3 years thereafter (annually for ACS participants >65y); all participants have imaging and fluid biomarker procedures at baseline and every 3 years thereafter. The Core is essential in that it supplies carefully characterized participants to all relevant Cores and Projects. The Clinical Core interacts directly or indirectly on a daily basis with virtually every facet of the ACS PPG. The functions of the Core are to: 1. Recruit, enroll, and maintain the ACS cohort at ~300 active participants to support the Projects in this application. Twenty-five new participants <65y will be enrolled each year to replenish the younger groups due to aging into the ≥65y group. 2. Comprehensively assess the ACS participants with well-established clinical and psychometric instruments at entry and every three years (annually for participants >65 years of age). With this application, the clinical instruments will be augmented with a questionnaire to assess social determinants of health. 3. Obtain blood from all participants for apolipoprotein E (APOE) genotyping and banking of extracted DNA and plasma (supported by the Knight ADRC Genetics and High Throughput –Omics Core with costs covered by ACS). 4. Coordinate the participation of ACS participants in the procedures of the Fluid Biomarker Core and all Projects: Project 1 – Tau Burden and Spatial Spread in Preclinical Alzheimer Disease Project 2 – Plasma and CSF Biomarkers that Predict Risk for Symptomatic Alzheimer Disease Project 3 – Alzheimer Disease Progression, Host Gut Microbiome, and Enteric Dysfunction Project 4 – Mechanisms and Moderators of the Effects of Physical Activity in Preclinical Alzheimer Disease 5. Integrate all Core data with the DMBC, and interact cooperatively with all components of the PPG. 6. Encourage the retention of ACS participants by safeguarding their research data, monitoring the participants' burden as they complete the protocols of the Cores and Projects, annually sharing with them research results, and soliciting their input into the Aims and operations of the ACS.